The diagnostic accuracy of headache measurement instruments: A systematic review and meta-analysis focusing on headaches associated with musculoskeletal symptoms

Contains fulltext : 208202.pdf (publisher's version ) (Open Access)AIM: To systematically review the available literature on the diagnostic accuracy of questionnaires and measurement instruments for headaches associated with musculoskeletal symptoms. DESIGN: Articles were eligible for inclusion when the diagnostic accuracy (sensitivity/specificity) was established for measurement instruments for headaches associated with musculoskeletal symptoms in an adult population. The databases searched were PubMed (1966-2018), Cochrane (1898-2018) and Cinahl (1988-2018). Methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for criterion validity. When possible, a meta-analysis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) recommendations were applied to establish the level of evidence per measurement instrument. RESULTS: From 3450 articles identified, 31 articles were included in this review. Eleven measurement instruments for migraine were identified, of which the ID-Migraine is recommended with a moderate level of evidence and a pooled sensitivity of 0.87 (95% CI: 0.85-0.89) and specificity of 0.75 (95% CI: 0.72-0.78). Six measurement instruments examined both migraine and tension-type headache and only the Headache Screening Questionnaire - Dutch version has a moderate level of evidence with a sensitivity of 0.69 (95% CI 0.55-0.80) and specificity of 0.90 (95% CI 0.77-0.96) for migraine, and a sensitivity of 0.36 (95% CI 0.21-0.54) and specificity of 0.86 (95% CI 0.74-0.92) for tension-type headache. For cervicogenic headache, only the cervical flexion rotation test was identified and had a very low level of evidence with a pooled sensitivity of 0.83 (95% CI 0.72-0.94) and specificity of 0.82 (95% CI 0.73-0.91). DISCUSSION: The current review is the first to establish an overview of the diagnostic accuracy of measurement instruments for headaches associated with musculoskeletal factors. However, as most measurement instruments were validated in one study, pooling was not always possible. Risk of bias was a serious problem for most studies, decreasing the level of evidence. More research is needed to enhance the level of evidence for existing measurement instruments for multiple headaches

Genomic Islands Confer Heavy Metal Resistance in <i>Mucilaginibacter kameinonensis</i> and <i>Mucilaginibacter rubeus</i> Isolated from a Gold/Copper Mine.

Heavy metals (HMs) are compounds that can be hazardous and impair growth of living organisms. Bacteria have evolved the capability not only to cope with heavy metals but also to detoxify polluted environments. Three heavy metal-resistant strains of &lt;i&gt;Mucilaginibacer rubeus&lt;/i&gt; and one of &lt;i&gt;Mucilaginibacter kameinonensis&lt;/i&gt; were isolated from the gold/copper Zijin mining site, Longyan, Fujian, China. These strains were shown to exhibit high resistance to heavy metals with minimal inhibitory concentration reaching up to 3.5 mM Cu &lt;sup&gt;(II)&lt;/sup&gt; , 21 mM Zn &lt;sup&gt;(II)&lt;/sup&gt; , 1.2 mM Cd &lt;sup&gt;(II)&lt;/sup&gt; , and 10.0 mM As &lt;sup&gt;(III)&lt;/sup&gt; . Genomes of the four strains were sequenced by Illumina. Sequence analyses revealed the presence of a high abundance of heavy metal resistance (HMR) determinants. One of the strain, &lt;i&gt;M. rubeus&lt;/i&gt; P2, carried genes encoding 6 putative P &lt;sub&gt;IB-1&lt;/sub&gt; -ATPase, 5 putative P &lt;sub&gt;IB-3&lt;/sub&gt; -ATPase, 4 putative Zn &lt;sup&gt;(II)&lt;/sup&gt; /Cd &lt;sup&gt;(II)&lt;/sup&gt; P &lt;sub&gt;IB-4&lt;/sub&gt; type ATPase, and 16 putative resistance-nodulation-division (RND)-type metal transporter systems. Moreover, the four genomes contained a high abundance of genes coding for putative metal binding chaperones. Analysis of the close vicinity of these HMR determinants uncovered the presence of clusters of genes potentially associated with mobile genetic elements. These loci included genes coding for tyrosine recombinases (integrases) and subunits of mating pore (type 4 secretion system), respectively allowing integration/excision and conjugative transfer of numerous genomic islands. Further in silico analyses revealed that their genetic organization and gene products resemble the &lt;i&gt;Bacteroides&lt;/i&gt; integrative and conjugative element CTnDOT. These results highlight the pivotal role of genomic islands in the acquisition and dissemination of adaptive traits, allowing for rapid adaption of bacteria and colonization of hostile environments

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes